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# Co-Trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic consisting of trimethoprim and sulfamethoxazole, which act synergistically to inhibit bacterial folic acid synthesis. It is available in various formulations, including oral tablets, oral suspension, and intravenous injection. The ratio of trimethoprim to sulfamethoxazole is typically 1:5.
## Primary Indications
* Urinary tract infections (UTIs), including acute uncomplicated cystitis and acute pyelonephritis
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Bacterial prostatitis
* Certain respiratory tract infections (e.g., acute exacerbations of chronic bronchitis, otitis media)
* Shigellosis and traveler's diarrhea
* *Staphylococcus aureus* infections, including some MRSA infections (though susceptibility should be confirmed)
## Adult Dosing
Dosing is based on the trimethoprim component, usually expressed as mg of TMP. The standard adult dose is 160 mg TMP / 800 mg SMX (1 DS tablet) every 12 hours.
* **UTIs:** 160 mg TMP / 800 mg SMX every 12 hours for 3-7 days (cystitis) or 7-14 days (pyelonephritis).
* **PCP Treatment:** 160 mg TMP / 800 mg SMX every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 160 mg TMP / 800 mg SMX once daily, or 80 mg TMP / 400 mg SMX twice daily, or 160 mg TMP / 800 mg SMX three times weekly (depending on local protocol and patient tolerance).
* **Shigellosis/Traveler's Diarrhea:** 160 mg TMP / 800 mg SMX every 12 hours for 5 days.
* **Prostatitis:** 160 mg TMP / 800 mg SMX every 12 hours for 4-6 weeks.
## Pediatric Dosing
Dosing is based on weight and indication, expressed as mg of TMP per kg per day, divided into two doses.
* **General Infections:** 15-20 mg TMP/kg/day divided every 12 hours.
* Example: For a 20 kg child, the dose would be 300-400 mg TMP/day divided every 12 hours.
* **PCP Treatment:** 20 mg TMP/kg/day divided every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 10 mg TMP/kg/day divided every 12 hours, or 15 mg TMP/kg/day given 3 times weekly on alternate days (depending on local protocol).
## Dose Adjustments
* **Renal Impairment (CrCl > 30 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl 15-30 mL/min):** Administer 75% of the standard dose.
* **Renal Impairment (CrCl < 15 mL/min):** Administer 50% of the standard dose or 25% of the standard dose every 12 hours. Consult prescribing information.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* Documented severe adverse reaction (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) to sulfonamides or trimethoprim.
* Diagnosis of megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Patients with severe renal or hepatic insufficiency if drug concentration cannot be monitored.
* **Pregnancy:** Generally avoided, especially in the third trimester due to risk of kernicterus.
## Adverse Effects
Common:
* Gastrointestinal: Nausea, vomiting, diarrhea, anorexia.
* Dermatologic: Rash (most common), pruritus.
* Hematologic: Leukopenia, thrombocytopenia, eosinophilia.
Serious:
* Severe dermatologic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
* Hypersensitivity reactions, including anaphylaxis.
* Hematologic abnormalities (agranulocytosis, aplastic anemia, purpura).
* Hepatitis, cholestatic jaundice.
* Hyperkalemia.
* Renal damage.
* Aseptic meningitis.
* *Clostridium difficile*-associated diarrhea.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and consider dose adjustments.
* **ACE Inhibitors / ARBs / Potassium-Sparing Diuretics / Potassium Supplements:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity (especially in high-dose methotrexate therapy).
* **Thiazide Diuretics:** Increased risk of thrombocytopenia, especially in elderly patients.
* **Cyclosporine:** Increased cyclosporine levels, potentially leading to nephrotoxicity.
* **Potassium:** Concurrent use can lead to hyperkalemia.
* **Potassium-rich foods/salt substitutes:** Increased risk of hyperkalemia.
* **Oral Hypoglycemics:** May potentiate the hypoglycemic effect.
* **Digoxin:** Increased digoxin levels.
## Monitoring
* **Renal function:** Monitor serum creatinine and BUN, especially in patients with renal impairment.
* **Electrolytes:** Monitor potassium levels, particularly in patients at risk for hyperkalemia.
* **Complete Blood Count (CBC):** Monitor for hematologic abnormalities, especially with prolonged therapy or in immunocompromised patients. Baseline and periodic monitoring are recommended.
* **Liver function tests:** Monitor if symptoms suggest hepatic dysfunction.
* **Therapeutic drug monitoring:** May be considered in specific situations (e.g., immunocompromised patients, suspected toxicity).
* **Signs of hypersensitivity reactions:** Monitor skin and mucous membranes.
## Clinical Pearls
* Ensure adequate hydration to minimize crystalluria.
* Co-trimoxazole can interfere with urine glucose and protein testing.
* Consider a folic acid supplement (e.g., 5-10 mg daily) for patients on long-term therapy, particularly those with megaloblastic anemia or risk factors, to prevent hematologic side effects, unless contraindicated.
* Discontinue co-trimoxazole immediately if a rash or other signs of hypersensitivity develop.
* May be used for MRSA skin infections, but susceptibility testing is crucial.
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*This information is intended for healthcare professionals. Always verify current prescribing information and consult with a pharmacist or physician for patient-specific guidance.*
